Advanced CancerPhase 1NCT04121676
Anti-CD137 and Anti-CTLA-4 Monoclonal Antibody in Patients With Advanced Cancer
A Phase 1 study testing AGEN2373 and Botensilimab in people with Advanced Cancer, run by Agenus Inc. at 12 sites in United States.
Trial summary
This study is an open-label, Phase 1, multicenter study to evaluate the safety, tolerability, PK, and PD profiles of AGEN2373 as a monotherapy and in combination with botensilimab (also known as AGEN1181), and to assess the maximum tolerated dose (MTD) in subjects with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer
- What is being tested?
- AGEN2373 and Botensilimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 91 participants
- Where
- 12 sitesUnited States
- Study dates
- 26 Sep 2019to 30 Nov 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study specific procedures. Participation in pharmacogenomics testing is optional.
- ≥ 18 years of age.
- Histologically or cytologically confirmed diagnosis of a solid tumor that is currently metastatic or locally advanced for which no standard therapy is available or standard therapy has failed.
- Measurable disease on imaging based on RECIST 1.1.
- Life expectancy of ≥ 3 months and ECOG performance status of 0 or 1.
- Adequate organ and bone marrow reserve function, as indicated by the following laboratory values:
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- Adequate hematological function, defined as absolute neutrophil count ≥ 1.5 × 10^9/L, platelet count ≥ 100 × 10^9/L, and hemoglobin ≥ 8 g/dL without recent transfusion (defined as a transfusion that has occurred within 2 weeks of the hemoglobin measurement)
- Adequate liver function, defined as total bilirubin level ≤ 1.5 × upper limit of normal (ULN), aspartate aminotransferase ≤ 2.5 × ULN, and alanine aminotransferase ≤ 2.5 × ULN, albumin ≥ 3 g/dL, and alkaline phosphatase ≤ 2.5 × ULN or ≤ 5 × ULN for patients with liver metastases
- Adequate renal function defined as creatinine ≤ 1.5 × ULN OR measured or calculated creatinine clearance ≥ 40 mL/minute per institutional standard. Assessment methods should be recorded
- Adequate coagulation, defined as international normalized ratio or prothrombin time ≤ 1.5 × ULN and activated partial thromboplastin time ≤ 1.5 × ULN (unless patient is receiving anticoagulant therapy)
- Patients with a history of prior malignancy are eligible if treatment was completed ≥ 2 years prior to the first dose of study treatment and the patient has no evidence of disease.
- Patients must provide a sufficient and adequate formalin-fixed paraffin-embedded tumor tissue sample (biopsy) collected after the last dose of prior anti-cancer therapy and before the first dose of study treatment from a site not previously irradiated and agree to mandatory on-treatment biopsy if clinically feasible.
- Female patients of childbearing potential must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication). Non-childbearing potential is defined as 1 of the following:
- ≥ 45 years of age and has not had menses for > 1 year
- Amenorrheic for > 2 years without a hysterectomy and oophorectomy and follicle-stimulating hormone value in the postmenopausal range upon prestudy (screening) evaluation
- Status is post-hysterectomy, -bilateral oophorectomy, or -tubal ligation
- Female patients of childbearing potential must be willing to use highly effective contraceptive measures starting with the Screening Visit through 90 days after last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception method for the patient.
- Male patients with a female partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the study starting with the Screening Visit through 90 days after the last dose of study treatment is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner. Note: Abstinence is acceptable if this is the established and preferred contraception method for the patient.
- Specific Melanoma Criteria:
- Note: these specific criteria below are in addition to the general criteria above and supersede the general criteria in some cases.
- Histological confirmation of cutaneous melanoma.
- Progression on or within 24 weeks of stopping treatment with a PD-1/PD-L1 confirmed per Society for Immunotherapy of Cancer (SITC).
- Patients with BRAF V600-positive tumor(s) should also have received prior treatment with a BRAF inhibitor (alone or in combination with a MEK inhibitor) or have declined targeted therapy.
- Note: Patients with BRAF V600-positive tumors with no clinically significant tumor-related symptoms nor evidence of rapidly progressive disease are not required to be treated with a BRAF inhibitor (alone or in combination with a MEK inhibitor) based on Investigator's decision.
Who cannot join
- Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 3 weeks of first dose of current study treatment.
- Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or major surgery outside of the acceptable washout period prior to first dose of study drug. A 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease, with Sponsor approval.
- The following washout windows are acceptable from prior treatments (i.e., patients with time periods less than the following should be excluded):
- Cytotoxic agent ≥ 3 weeks is acceptable (i.e., < 3 weeks should be excluded)
- Monoclonal antibodies ≥ 4 weeks is acceptable (i.e., < 4 weeks should be excluded)
- Proteasome inhibitors or corticosteroids ≥ 2 weeks is acceptable (i.e., < 2 weeks should be excluded)
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- Small molecule/tyrosine kinase inhibitor within 14 days or less than 5 circulating half-lives of investigational drug
- Having a previous SARS-CoV-2 vaccine > 7 days before administration. For vaccines requiring more than 1 dose, the full series should be completed prior to Cycle 1 Day 1, when feasible, and when the delay in initiation of study treatment would not put the study patients at risk
- Patients who have received prior anti-CD137 therapy may be enrolled upon agreement with the Sponsor.
- Persistent toxicity of NCI-CTCAE version 5.0 Grade > 1 severity that is related to prior therapy. Note: Sensory neuropathy or alopecia of Grade ≤ 2 are acceptable.
- Expected to require any other form of systemic or localized antineoplastic therapy while on study (including maintenance therapy with another agent, radiation therapy, and/or surgical resection).
- History of:
- Severe (Grade ≥ 3) hypersensitivity reactions to fully human monoclonal antibodies
- Immune-related adverse event requiring treatment with systemic steroids for > 7 days (refer to Exclusion Criterion #7 for exceptions) excluding Grade 1 or 2 rash
- Interstitial lung disease or lung disease which may interfere with the assessment of pneumonitis
- Uncontrolled asthma (i.e., ≥ 3 features of partly controlled asthma)
- Pneumonitis that has required oral or IV corticosteroids
- Receiving systemic corticosteroid therapy per Exclusion Criterion #2, or any other form of systemic immunosuppressive medication. Note: Corticosteroid use as a premedication for IV contrast allergies/reactions is allowed. Patients who are receiving daily corticosteroid replacement therapy are also an exception to this rule. Daily prednisone at doses of ≤ 10 mg or equivalent hydrocortisone dose are examples of permitted replacement therapy. Use of inhaled or topical corticosteroids is permitted.
- CNS tumor, metastasis(es), and/or carcinomatous meningitis identified either on the baseline brain imaging obtained during the Screening Period or identified prior to consent. Note: Patients with history of brain metastases that have been treated may participate provided they show evidence of stable supra-tentorial lesions at screening (defined as 2 brain images, both of which are obtained after treatment to the brain metastases and obtained ≥ 4 weeks apart). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have returned to baseline or resolved. Any steroids administered as part of this therapy must be completed ≥ 3 days prior to first dose of study medication.
- Active or history of autoimmune disease that requires systemic treatment within 2 years of the start of study treatment (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Note: Patients with autoimmune conditions requiring hormone replacement therapy or topical treatment are eligible.
- Has had an allogeneic tissue/solid organ transplant except for corneal transplantation.
- Active infection requiring systemic treatment.
- Active infection with HIV and CD4+ T-cell count <350/μL. Patients not on established antiretroviral therapy for at least 4 weeks and having a detectable HIV viral load. Testing is not required for eligibility.
- Active infection with hepatitis B (surface antigen); or infection with hepatitis C, defined by a detectable viral load. Testing is required for eligibility only if patient has a known or suspected history of infection.
- Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure (New York Heart Association class ≥ II), or serious uncontrolled cardiac arrhythmia requiring medication.
- History or current evidence of any condition, therapy, any active infections, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
- Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
- Legally incapacitated or has limited legal capacity.
- Pregnant or breastfeeding.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
Roswell Park Comprehensive Cancer Care
Buffalo, New York, 14203
University of Miami
Coral Gables, Florida, 33146
Mary Crowley Cancer Research Center
Dallas, Texas, 75230
University of Southern California Norris Comprehensive Cancer Center/ Hoag
Los Angeles, California, 90033
Atlantic Health System
Morristown, New Jersey, 07960
Columbia University
New York, New York, 10032
UPMC
Pittsburgh, Pennsylvania, 15232
Providence Cancer Institute
Portland, Oregon, 97213
NEXT Oncology
San Antonio, Texas, 78229
University of Washington
Seattle, Washington, 98109
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: A Phase 1 Study of AGEN2373, an Anti-CD137 Monoclonal Antibody, as Monotherapy and in Combination With AGEN1181, an Fc-Engineered Anti-CTLA-4 Monoclonal Antibody, in Patients With Advanced Cancer
This study is an open-label, Phase 1, multicenter study to evaluate the safety, tolerability, PK, and PD profiles of AGEN2373 as a monotherapy and in combination with botensilimab (also known as AGEN1181), and to assess the maximum tolerated dose (MTD) in subjects with advanced solid tumors.
Read the detailed description
This Phase 1 study will enroll up to approximately 200 evaluable adult patients with a histologically confirmed diagnosis of advanced cancer for which no standard therapy is available or standard therapy has failed, regardless of diagnosis and prior therapies. This also includes patients with PD-1/PD-L1 R/R melanoma. Patients may be enrolled into one of 5 treatment arms:
2-Week AGEN2373 monotherapy
3-Week AGEN2373 monotherapy
4-Week AGEN2373 monotherapy
Combination of AGEN2373 and botensilimab in patients with programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) relapsed/refractory (R/R) melanoma.
Group 1 (Monotherapy Lead-in Combination): AGEN2373 will be administered every 3 weeks (Q3W). Starting on Cycle 4, AGEN1181 will be administered on Day 1 of every other 3-week cycle (Cycles 4, 6, 8, etc.) in combination with AGEN2373.
Group 2 (Combination): AGEN2373 will be administered Q3W in combination with botensilimab administered every other cycle.
The trial will consist of a 3+3 dose escalation that will evaluate different combination dose levels of AGEN2373 monotherapy and in combination with botensilimab. Each patient will stay on the dose level and schedule assigned at trial entry. Treatment with AGEN2373 monotherapy will be up to 2 years (i.e., maximum of 34 cycles). For combination therapy, AGEN1181 will be continued up to 1 year (i.e., maximum of 8 doses) and for AGEN2373 up to 2 years (i.e., maximum of 34 cycles), or until unacceptable toxicity, disease progression, consent is withdrawn, or any criterion for stopping the study drug or withdrawal of trial occurs.
Patients who do not complete the DLT observation period (28 days for the 2-Week and 4-Week AGEN2373 Monotherapy arms and 21 days for the 3-Week AGEN2373 Monotherapy and Combination arms) after the first dose for reasons other than DLT will be replaced.
- Conditions
- Advanced Cancer
- Being tested
- AGEN2373, Botensilimab
- Keywords
- Combination Therapy, Anti-CD137, Anti-CTLA-4, Single Agent, Monotherapy, Melanoma, Cutaneous Melanoma, Solid Tumors, Advanced Cancer, Open-Label, Dose Escalation, 4-1BB
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AGEN2373Drug
Also called Anti-CD137
An Anti-CD137 Monoclonal Antibody
BotensilimabDrug
Also called AGEN1181, Anti-CTLA-4
Anti-CTLA-4 Monoclonal Antibody
| Study group | Role | What they receive |
|---|---|---|
| 2-Week Monotherapy with AGEN2373 | Experimental | 3+3 Dose escalation of AGEN2373 administered by IV. Receives: Drug: AGEN2373 |
| 3-Week Monotherapy with AGEN2373 | Experimental | 3+3 Dose escalation of AGEN2373 administered by IV. Receives: Drug: AGEN2373 |
| 4-Week Monotherapy with AGEN2373 | Experimental | 3+3 Dose escalation of AGEN2373 administered by IV. Receives: Drug: AGEN2373 |
| Combination Therapy with 3-week AGEN2373 Monotherapy Lead-In Combination with 6-week Botensilimab | Experimental | 3+3+3 Dose escalation of AGEN2373. AGEN2373 and botensilimab administered by IV. Receives: Drug: AGEN2373; Drug: Botensilimab |
| Combination Therapy with 3-week AGEN2373 in combination with 6-week Botensilimab | Experimental | 3+3+3 Dose escalation of AGEN2373. AGEN2373 and botensilimab administered by IV. Receives: Drug: AGEN2373; Drug: Botensilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of Dose Limiting Toxicity (DLT)
DLT in patient in dose escalation phase
Measured: First 28 days of treatment Q2W and Q4W and First 21 days Q3W
Frequency of treatment-emergent adverse events (TEAEs)
According to NCI-CTCAE Version 5.0, vital signs (blood pressure, heartrate, and temperature), physical examinations, 12-lead electrocardiogram, Eastern Cooperative Oncology Group (ECOG) performance status, and clinical laboratory assessments for all dose groups
Measured: Screening to 90 days from last dose
Severity of treatment-emergent adverse events (TEAEs)
According to NCI-CTCAE Version 5.0, vital signs (blood pressure, heartrate, and temperature), physical examinations, 12-lead electrocardiogram, Eastern Cooperative Oncology Group (ECOG) performance status, and clinical laboratory assessments for all dose groups
Measured: Screening to 90 days from last dose
Duration of treatment-emergent adverse events (TEAEs)
According to NCI-CTCAE Version 5.0, vital signs (blood pressure, heartrate, and temperature), physical examinations, 12-lead electrocardiogram, Eastern Cooperative Oncology Group (ECOG) performance status, and clinical laboratory assessments for all dose groups
Measured: Screening to 90 days from last dose
Secondary outcomes (15)
Maximum observed concentration at steady state (Cmax-ss)
PK Profile of AGEN2373 and botensilimab
Measured: Day 1 of dosing through 90 days from the last dose
Minimum observed concentration at steady state (Cmin-ss)
PK Profile of AGEN2373 and botensilimab
Measured: Day 1 of dosing through 90 days from the last dose
Area under the plasma/serum concentration-time curve within time span t1 to t2 at steady-state (AUC(t1-t2)-ss)
PK Profile of AGEN2373 and botensilimab
Measured: Day 1 of dosing through 90 days from the last dose
Area under the plasma/serum concentration-time curve from time zero to time t (AUC(0-t))
PK Profile of AGEN2373 and botensilimab
Measured: Day 1 of dosing through 90 days from the last dose
Area under the plasma/serum concentration-time curve from time zero to infinity (AUC(0-∞))
PK Profile of AGEN2373 and botensilimab
Measured: Day 1 of dosing through 90 days from the last dose
Time to maximum observed concentration (tmax)
PK Profile of AGEN2373 and botensilimab
Measured: Day 1 of dosing through 90 days from the last dose
Terminal disposition rate constant (λz)
PK Profile of AGEN2373 and botensilimab
Measured: Day 1 of dosing through 90 days from the last dose
Terminal elimination half-life (t1/2)
PK Profile of AGEN2373
Measured: Day 1 of dosing through 90 days from the last dose
Systemic clearance (CL)
PK Profile of AGEN2373 and botensilimab
Measured: Day 1 of dosing through 90 days from the last dose
Volume of distribution (Vd)
PK Profile of AGEN2373 and botensilimab
Measured: Day 1 of dosing through 90 days from the last dose
Immunogenicity of AGEN2373
ADA Profile of AGEN2373 and botensilimab
Measured: Pre-dose through 3 months after the last dose
Overall Response Rate (ORR)
per RECIST 1.1
Measured: Evaluated throughout the protocol up to 2 years
Duration of Response (DOR)
per RECIST 1.1
Measured: First observation of documented disease progression (or death within 12 weeks of the last tumor assessment)
Disease Control Rate (DCR)
including complete and partial responders and stable disease [SD] for at least 12 weeks per RECIST 1.1
Measured: Time Frame: 24 weeks of first dose
Progression Free Survival (PFS)
median and/or rate as defined in the statistical analysis plan
Measured: First treatment administration to first observation of documented disease progression (or death within 12 weeks of last tumor assessment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2019
- Study start26 Sep 2019
- Primary completion22 Feb 2024
- Study completion30 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Dose escalation
- Masking
- None (open label)
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- Agenus Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Agenus Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04121676
- Sponsor's protocol ID
- C-1100-01
- Status last verified
- Jan 2025
- First submitted
- 2 Oct 2019
- Last updated
- 13 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Singh R, Kim YH, Lee SJ, Eom HS, Choi BK. 4-1BB immunotherapy: advances and hurdles. Exp Mol Med. 2024 Feb;56(1):32-39. doi: 10.1038/s12276-023-01136-4. Epub 2024 Jan 4.
PubMed 38172595
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of AGEN2373, an Anti-CD137 Monoclonal Antibody, as Monotherapy and in Combination With AGEN1181, an Fc-Engineered Anti-CTLA-4 Monoclonal Antibody, in Patients With Advanced Cancer
- ClinicalTrials.gov ID
- NCT04121676
- Acronym / sponsor ID
- C-1100-01
- Conditions
- Advanced Cancer
- Keywords
- Combination Therapy, Anti-CD137, Anti-CTLA-4, Single Agent, Monotherapy, Melanoma, Cutaneous Melanoma, Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- Agenus Inc.Industry (pharma, biotech, devices)
- Study start
- 26 Sep 2019 (actual)
- Primary completion
- 22 Feb 2024 (actual)
- Study completion
- 30 Nov 2024 (actual)
- First posted
- 10 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is an open-label, Phase 1, multicenter study to evaluate the safety, tolerability, PK, and PD profiles of AGEN2373 as a monotherapy and in combination with botensilimab (also known as AGEN1181), and to assess the maximum tolerated dose (MTD) in subjects with advanced solid tumors.
Detailed description
This Phase 1 study will enroll up to approximately 200 evaluable adult patients with a histologically confirmed diagnosis of advanced cancer for which no standard therapy is available or standard therapy has failed, regardless of diagnosis and prior therapies. This also includes patients with PD-1/PD-L1 R/R melanoma. Patients may be enrolled into one of 5 treatment arms:
2-Week AGEN2373 monotherapy
3-Week AGEN2373 monotherapy
4-Week AGEN2373 monotherapy
Combination of AGEN2373 and botensilimab in patients with programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) relapsed/refractory (R/R) melanoma.
Group 1 (Monotherapy Lead-in Combination): AGEN2373 will be administered every 3 weeks (Q3W). Starting on Cycle 4, AGEN1181 will be administered on Day 1 of every other 3-week cycle (Cycles 4, 6, 8, etc.) in combination with AGEN2373.
Group 2 (Combination): AGEN2373 will be administered Q3W in combination with botensilimab administered every other cycle.
The trial will consist of a 3+3 dose escalation that will evaluate different combination dose levels of AGEN2373 monotherapy and in combination with botensilimab. Each patient will stay on the dose level and schedule assigned at trial entry. Treatment with AGEN2373 monotherapy will be up to 2 years (i.e., maximum of 34 cycles). For combination therapy, AGEN1181 will be continued up to 1 year (i.e., maximum of 8 doses) and for AGEN2373 up to 2 years (i.e., maximum of 34 cycles), or until unacceptable toxicity, disease progression, consent is withdrawn, or any criterion for stopping the study drug or withdrawal of trial occurs.
Patients who do not complete the DLT observation period (28 days for the 2-Week and 4-Week AGEN2373 Monotherapy arms and 21 days for the 3-Week AGEN2373 Monotherapy and Combination arms) after the first dose for reasons other than DLT will be replaced.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- Dose escalation
| Arm | Type | Receives |
|---|---|---|
| 2-Week Monotherapy with AGEN2373 | Experimental | Drug: AGEN23733+3 Dose escalation of AGEN2373 administered by IV. |
| 3-Week Monotherapy with AGEN2373 | Experimental | Drug: AGEN23733+3 Dose escalation of AGEN2373 administered by IV. |
| 4-Week Monotherapy with AGEN2373 | Experimental | Drug: AGEN23733+3 Dose escalation of AGEN2373 administered by IV. |
| Combination Therapy with 3-week AGEN2373 Monotherapy Lead-In Combination with 6-week Botensilimab | Experimental | Drug: AGEN2373, Drug: Botensilimab3+3+3 Dose escalation of AGEN2373. AGEN2373 and botensilimab administered by IV. |
| Combination Therapy with 3-week AGEN2373 in combination with 6-week Botensilimab | Experimental | Drug: AGEN2373, Drug: Botensilimab3+3+3 Dose escalation of AGEN2373. AGEN2373 and botensilimab administered by IV. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study specific procedures. Participation in pharmacogenomics testing is optional.
- ≥ 18 years of age.
- Histologically or cytologically confirmed diagnosis of a solid tumor that is currently metastatic or locally advanced for which no standard therapy is available or standard therapy has failed.
- Measurable disease on imaging based on RECIST 1.1.
- Life expectancy of ≥ 3 months and ECOG performance status of 0 or 1.
Key exclusion criteria (29 listed)
- Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 3 weeks of first dose of current study treatment.
- Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or major surgery outside of the acceptable washout period prior to first dose of study drug. A 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease, with Sponsor approval.
- The following washout windows are acceptable from prior treatments (i.e., patients with time periods less than the following should be excluded):
- Patients who have received prior anti-CD137 therapy may be enrolled upon agreement with the Sponsor.
- Persistent toxicity of NCI-CTCAE version 5.0 Grade > 1 severity that is related to prior therapy. Note: Sensory neuropathy or alopecia of Grade ≤ 2 are acceptable.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AGEN2373Also: Anti-CD137An Anti-CD137 Monoclonal Antibody | Drug | 2-Week Monotherapy with AGEN2373, 3-Week Monotherapy with AGEN2373, 4-Week Monotherapy with AGEN2373, Combination Therapy with 3-week AGEN2373 Monotherapy Lead-In Combination with 6-week Botensilimab, Combination Therapy with 3-week AGEN2373 in combination with 6-week Botensilimab |
| BotensilimabAlso: AGEN1181, Anti-CTLA-4Anti-CTLA-4 Monoclonal Antibody | Drug | Combination Therapy with 3-week AGEN2373 Monotherapy Lead-In Combination with 6-week Botensilimab, Combination Therapy with 3-week AGEN2373 in combination with 6-week Botensilimab |
Primary outcome
Occurrence of Dose Limiting Toxicity (DLT)
Time frame: First 28 days of treatment Q2W and Q4W and First 21 days Q3W
DLT in patient in dose escalation phase
Frequency of treatment-emergent adverse events (TEAEs)
Time frame: Screening to 90 days from last dose
According to NCI-CTCAE Version 5.0, vital signs (blood pressure, heartrate, and temperature), physical examinations, 12-lead electrocardiogram, Eastern Cooperative Oncology Group (ECOG) performance status, and clinical laboratory assessments for all dose groups
Severity of treatment-emergent adverse events (TEAEs)
Time frame: Screening to 90 days from last dose
According to NCI-CTCAE Version 5.0, vital signs (blood pressure, heartrate, and temperature), physical examinations, 12-lead electrocardiogram, Eastern Cooperative Oncology Group (ECOG) performance status, and clinical laboratory assessments for all dose groups
Duration of treatment-emergent adverse events (TEAEs)
Time frame: Screening to 90 days from last dose
According to NCI-CTCAE Version 5.0, vital signs (blood pressure, heartrate, and temperature), physical examinations, 12-lead electrocardiogram, Eastern Cooperative Oncology Group (ECOG) performance status, and clinical laboratory assessments for all dose groups
15 secondary outcomes
Maximum observed concentration at steady state (Cmax-ss)
Time frame: Day 1 of dosing through 90 days from the last dose
Minimum observed concentration at steady state (Cmin-ss)
Time frame: Day 1 of dosing through 90 days from the last dose
Area under the plasma/serum concentration-time curve within time span t1 to t2 at steady-state (AUC(t1-t2)-ss)
Time frame: Day 1 of dosing through 90 days from the last dose
Area under the plasma/serum concentration-time curve from time zero to time t (AUC(0-t))
Time frame: Day 1 of dosing through 90 days from the last dose
Area under the plasma/serum concentration-time curve from time zero to infinity (AUC(0-∞))
Time frame: Day 1 of dosing through 90 days from the last dose
Time to maximum observed concentration (tmax)
Time frame: Day 1 of dosing through 90 days from the last dose
Terminal disposition rate constant (λz)
Time frame: Day 1 of dosing through 90 days from the last dose
Terminal elimination half-life (t1/2)
Time frame: Day 1 of dosing through 90 days from the last dose
Systemic clearance (CL)
Time frame: Day 1 of dosing through 90 days from the last dose
Volume of distribution (Vd)
Time frame: Day 1 of dosing through 90 days from the last dose
Immunogenicity of AGEN2373
Time frame: Pre-dose through 3 months after the last dose
Overall Response Rate (ORR)
Time frame: Evaluated throughout the protocol up to 2 years
Duration of Response (DOR)
Time frame: First observation of documented disease progression (or death within 12 weeks of the last tumor assessment)
Disease Control Rate (DCR)
Time frame: Time Frame: 24 weeks of first dose
Progression Free Survival (PFS)
Time frame: First treatment administration to first observation of documented disease progression (or death within 12 weeks of last tumor assessment)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2025.
- Derived from this study: PubMed 38172595Singh R, Kim YH, Lee SJ, Eom HS, Choi BK. 4-1BB immunotherapy: advances and hurdles. Exp Mol Med. 2024 Feb;56(1):32-39. doi: 10.1038/s12276-023-01136-4. Epub 2024 Jan 4.
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Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Agenus Inc.
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AGEN2373 and Botensilimab in people with Advanced Cancer, run by Agenus Inc. at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of Dose Limiting Toxicity (DLT) (time frame: First 28 days of treatment Q2W and Q4W and First 21 days Q3W). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04121676, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2025.